Faced with a novel food, an animal is confronted with a decision that cannot be taken lightly. While ingestion of the food may lead to a nutritious meal, it may, if the food is poisonous, cause death. Powerful learning processes have evolved to guide ingestive behavior. The most important of these processes, conditioned taste aversion (CTA) learning, not only prevents the repeated ingestion of toxic food, and therefore has wide reaching implications for dietary choices in everyday life, but also is implicated in many other situations relevant to our well being. For instance, cancer patients oftentimes develop strong aversions to their diets (leading to anorexia and cachexia) because the aversive visceral side effects of chemotherapy are associated with the foods consumed before treatment. Our research encourages the view that the absence of CTA in chronic decerebrate rats is the inadvertent consequence of a decerebration-induced functional loss of neurons in the parabrachial nucleus (PBN). Indeed, we believe that the PBN is the single most important brain structure for CTA learning and that the forebrain contributes to the PBN associative mechanism by modulating the perception of taste novelty/familiarity. The goals of the proposed research are to: (1) determine the pharmacological substrates of CTA learning in the PBN and (2) establish the roles of forebrain structures in taste novelty perception. The research of our first goal utilizes intraPBN drug infusions to determine whether CTA acquisition and/or reconsolidation is a protein synthesis- (Specific Aim 1) and/or a glutamate receptor- (Specific Aim 2) dependent process in the PBN. The research of our second short-term goal will investigate the roles of forebrain structures (insular cortex, basolateral amygdala and medial amygdala) in a novelty recognition procedure (taste neophobia) using a disconnection strategy involving asymmetric lesions (Specific Aim 3) or temporary inactivation (Specific Aim 4). By studying the behavioral breakdowns consequent to the stated brain manipulations, we expect to make significant progress in our long-term goal of defining the neural system responsible for CTA learning. PUBLIC HEALTH RELEVANCE: Conditioned taste aversions (CTAs), which are rapidly acquired when ingestion of a novel food is followed by gastrointestinal malaise, are manifest as a diminished intake of that food on subsequent encounters. Understanding the neural substrates of this profoundly important learning process will yield insights into the neural integration of gustatory and visceral functions and may provide a foundation for the development of treatments and interventions that might ameliorate, for example, the unwanted, and oftentimes debilitating, nutritional side effects of invasive medical therapies such as chemo- or radiation therapy for cancer.